This program project is the plan of a group of investigators joined together by mutual interest in the hemoglobin--red blood cell system of man. By sharing knowledge, "know-how" methodologies and approaches, equipment and other facilities and by continuing and close communication of individual research progress, problems and insights, the associated investigators seek to achieve new understanding of the structural and functional interrelationship between hemoglobin, the red cell membrane and the red cell as a whole in the normal state and in abnormal conditions such as sickle cell disease and other hemoglobinopathies. Our attention will be directed towards the electronic states of the heme group, structure and structural kinetic (motility) and associative behavior of hemoglobin, the ligand binding properties of hemoglobin and linked functions, the effect of alterations in hemoglobin structure and structural behavior on the red cell membrane and the red cell as a whole, the flow properties of red cells, their sorting and their deformability and reversible and irreversible deformations of cell and membrane. The intimate details of this chain of structure-function relationships between heme group, hemoglobin, membrane and cell will be thoroughly explored and defined. A wide spectrum of approaches will be used in the conjoint study. The ultimate mutual objectives will be a complete description of how alterations in primary structure of hemoglobin, such as that of hemoglobin S, result in alterations in function and form of membrane and cell and indeed, in all the complex manifestations that make up the disease state.